60-yr-old mystery behind Vel blood group solved

Researchers have finally uncovered the gene behind a human blood group that has remained a mystery for the past 60 years, a finding that could help make blood safer for hundreds of thousands of people worldwide.
They showed that a genetic deletion on this gene is responsible for the lack of this blood group in some people.
It is estimated that one in 5000 people are Vel-negative, and routine blood transfusions for patients with antibodies against Vel can lead to kidney failure and even death.
With the discovery of the gene behind the Vel blood group, medical scientists can now develop a more reliable DNA test to identify people who lack this group.

This will reduce the risk of severe, and sometimes life threatening, destruction of the Vel-positive donor red blood cells in patients with antibodies against Vel.
The genetic basis of nearly all 34 blood group systems has been resolved over the past century, but identification of the underlying gene of the Vel blood group has withstood persistent attempts since it was first identified 60 years ago.

"This is really exciting as it shows how the power of modern genomics technologies can directly benefit patient care," said Professor Willem Ouwehand, who heads one of the NHS Blood and Transplant research teams at both the University of Cambridge and the Wellcome Trust Sanger Institute in UK.

Researchers identified 65 individuals who lacked the Vel blood group by testing the red blood cells from nearly 350,000 donors with antibodies against Vel.
They then sequenced the coding fraction of the genomes of five donors who lack the Vel group to identify the underlying gene.
The team showed that the gene SMIM1 malfunctions in Vel-negative people. SMIM1 is found on chromosome 1 and specifies a small protein, five times smaller than the average human protein.
This provides a direct explanation why a discovery by other routes has proven so challenging, researchers said.
"We already knew of 75 genomic regions that are associated with the haemoglobin levels and other red blood cell traits, but we quickly realised that the SMIM1 gene identified in our study is the same as one of these associated regions," said Dr Pim van der Harst from Groningen University.

"We have shown that this gene controls a protein in the membrane of red blood cells. Switching off the SMIM1 gene in zebrafish showed a remarkable reduction in the number of red cells formed and caused anaemia in the fish," said Harst.
The team observed that the common variant identified by the red blood cell study has a strong effect on how well the SMIM1 gene functions.
This not only explains why the level of the Vel blood group varies so extensively in the population, but is also makes it extremely plausible that the Smim1 protein influences hemoglobin levels of red blood cells.